1. Field of the Invention
The present invention relates generally to analysis of LC-MS data, and more particularly to methods for temporal alignment of data files representative of chromatographic surfaces.
2. Description of the Related Art
Mass spectrometry has become a key analytical tool for studies in the field of proteomics. In such studies, different samples containing collections of proteins are separately analyzed in a mass spectrometer, and the resultant mass spectral data are compared in order to, for example, identify differential expression of one or more proteins that may be indicative of a disease state. Because the samples often contain complex mixtures comprising numerous component species, liquid chromatography is often employed to provide temporal separation of the different species and thereby simplify the interpretation of the mass spectral data. A problem associated with the use of LC-MS for proteomics studies arises from the inherent variability of chromatographic separation. Due to column aging and changes in experimental conditions, the time after injection at which a known species elutes from the column and is introduced into the mass spectrometer is not constant, but instead will vary from one chromatographic run to the next. Furthermore, the shift in elution times is not static, but instead changes from one species to another. This phenomenon is often referred to in the art as “time warping”, and must be accounted for and corrected when performing comparisons of mass spectral data.
A number of approaches are disclosed in the prior art for identifying and correcting chromatographic time warping (hereinafter referred to as alignment techniques). Earlier alignment techniques have focused on alignment of HPLC and gas phase chromatographic profiles where elution dynamics of only base peaks (the major features of the chromatogram) are considered. These techniques disregard other peaks of full mass scans. Methods that have been developed for alignment of chromatographic profiles include dynamic time warping (DTW), correlation-optimized warping (COW), parametric time warping, and parallel factor analysis. A salient characteristic of these methods is that they are designed to align two-dimensional chromatographic profiles, in which one dimension is time and the other is the measured base peak intensity; such methods do not comprehensively use mass informatics information (the mass-to-charge or m/z values of the detected ions) for the alignment calculation. The primary drawback of techniques of this general description is that they tend to align the most intense peaks in the chromatograms without regard to the mass origin of the peaks, which may lead to erroneous results.
More recently, chromatographic alignment techniques have been developed which comprehensively utilize mass informatics information to produce more reliable and accurate alignment of data files One such technique (see J. T. Prince and E. M. Marcotte, Chromatographic Alignment of Multi-Dimensional Mass Spectra using Interpolated Dynamics Time Warping, 53rd ASMS Conference, San Antonio, Tex., 2005) involves the use of correlation or dot product analysis between full MS scans to generate a correlation matrix and identify an optimal path. It has been found, however, that this technique works well only where the chromatographic time shifts are relatively small. For large chromatographic shifts, this technique may involve excessive computational expense and/or may result in paths that provide inaccurate alignment.